NONLINEAR MIXED EFFECTS MODELS IN PHARMACOKINETICS

用于纵向或重复测量分析的非线性模型 数据一直是密集的生物统计学研究领域。生物学上的， 临床试验，特别是药物计量学的应用在很大程度上 推动了这项研究。典型地，个体充当样本 单位，以及对相同或相关结果衡量的重复测量 在连续的时间点聚集在一起。对象内部的可变性 个体使用固定效果和随机误差进行建模，而 随机系数被用来模拟个体之间的变异性。 通常只对大量个体进行几次重复测量 是可计量的，因此需要采用合并估计法。在 制药行业主要关注的是非线性 药物浓度的隔室模型。 我们建议将最新的和正在进行的非线性混合 将特效建模集成到综合软件S+中。 将该软件专门用于药物计量领域。我们提出了一个 用于分析药物计量数据的综合模块，包括 预定义模型库，易于使用的图标图形用户 为分区建模和扩展模型设计的界面 诊断统计数据。在构建该软件的过程中，我们 建议从以下几个领域商业化实施新模式 非线性混合效应建模的研究现状。 建议的商业应用 拥有统计学或统计学学位的毕业生占很大比例 生物统计学应用于制药行业，在该行业 药物计量学模型具有重要意义。数量多得多的 药理学家也在同一领域开展工作。建议的模块提供 令人兴奋的新维度，它有许多易于使用的功能，将 让它在用户中相当受欢迎。MathSoft打算将目标对准 生物医药和生物制药市场。这些市场中的每个 代表数以万计的潜在用户。

Nonlinear models for the analysis of longitudinal or repeated measures data have been an area of intense biostatistical research. Biological, clinical trial, and especially pharmacometric applications have largely driven this research. Typically the individual serves as the sampling unit, and repeated measurements of the same or related outcome measures are gathered at successive time points. Variability within an individual is modeled using fixed effects and random errors, while random coefficients are used to model variability between individuals. Often only a few repeated measurements on a large number of individuals are measured, so pooled estimation methods are required. In the pharmaceutical industry concern is primarily with the nonlinear compartmental modeling of drug concentrations. We propose to incorporate recent and ongoing advances in nonlinear mixed effects modeling into comprehensive software integrated into S-PLUS. Specializing this software to the pharmacometric arena. We propose a comprehensive module for the analysis of pharmacometric data containing a library of predefined models, an easy to use iconic graphical user interface designed for compartmental modeling, and extensive model diagnostics statistics. In the process of building this software, we propose to commercially implement new models from several areas of current research in nonlinear mixed effects modeling. PROPOSED COMMERCIAL APPLICATION A large percentage of all graduates with degrees in statistics or biostatistics are employed in the pharmaceutical industry where pharmacometric models are of great importance. A much larger number of pharmacologists work in the same area. The proposed module offers exciting new dimensions and it has many ease-of-use features that will make it quite popular with users. MathSoft intends to target the biomedical and biopharmaceutical markets. Each of these markets represents tens of thousands of potential users.